Pulmonary (part 2) Flashcards
___ ___ is the most common lethal genetic disorder of white people
Cystic Fibrosis
Cystic fibrosis affects ____ people worldwide
70,000
In the U.S, there are ____ people with CF
30,000
Cystic fibrosis is an ___ ___ disorder
Autosomal recessive
CF is caused by a gene defect where there is a lack or a malfunction of _____ gene
CFTR
CFTR regulates the movement of ___ and ___ within cells in the airway
Cl- and HCO3
A mutation in CFTR gene causes…
-Defective Cl- and HCO3 secretion
-Enhanced Na+ reabsorption
The defects caused by CFTR mutation cause…
-Dehydrated secretions (not mobilized)
-Promoties bacterial infection
-Airways become colonized
Class I of CF (G542X) causes ____ ___ of CFTR
No synthesis
Class II of CF (F508del) causes ___ ___ of the CFTR gene, leading to an absense of functional protein at the cell membrane
Reduced trafficking
Class III of CF (G551D) causes ___ ___, so CFTR reaches the cell membrane, but becomes unstable
Reduced gating
Class IV CF (R117H) causes ___ ___, so CFTR reaches the cell membrane, but abnormal conformation of the pore leads to disrupted ion flow
Decreased conductance
Class V CF (A455E) causes ___ ___ of CFTR
Reduced synthesis
There are over ____ mutations of the CFTR gene, all with varying severity of disease
2000
If someone had an increased sweat ____, check for genotype and categorize to guide treatment
Chloride
In class I, there is…
No functional CFTR created
In class II, CFTR is created but ____ so it does not reach the surface
Misfolded
In classes III and IV, CFTR is created, but does not move through the ____ properly
Channel
In class V, there is inefficient ____, causing little or no CFTR production
Splicing
With minimal/no CFTR function, someone might experience…
-Chronic sinusitis
-Severe chronic infection
-Hepatobiliary disease
-CF-related diabetes
-GI: poor absorption of nutrients
-Male infertility
With partially effective CFTR function, someone might experience…
-Chronic sinusitis
-Chronic infection
-Normal hepatobiliary function
-Pancreatitis
-Normal or minimal problems
-Male infertility
The medial survival age for a child born with CCF in 2019 is ____ years
48
No other lung disease has seen such a dramatic ___ over time than CF
Improvement
What are we doing right for CF?
-CF centers: nationwide care model
-Newborn screening
-Family-clinician partnerships
-CF foundation- education and research
-High % participate in clinical trials
Since 2011, there have been ___ new drug targets for CFTR malfunction
3
____ is a potentiator drug that increases the time it takes for the CFTR channel to open
Ivacaftor (Kalydeco)
Ivacaftor (Kalydeco) has been shown to only be effective for CF class ___
III (G55ID)
Triple therapy includes ____ ____ and a ____; this has been effective for about 90% of patients for 6 or more years
2 correctors; potentiator
One example of a triple therapy is ____
Trikafta
Outcomes of Tricofta:
-Increased forced expiratory volume
-Decreased sweat chloride
-No dose-limiting side effects
The purpose of “vest” therapy is to ___ ___
Mobilize sputum
Vest therapy utilizes ___ ___ ___ ___ ___
High-frequency chest wall oscillation (HFCWO)
Vest therapy has shown to be highly effective in ____ ____
Secretion removal
We want to decrease ____ of the secretions in the lungs to reduce sputum-colonized bacteria
Viscosity
To control infection, ____ are recruited and release DNA filaments covered with neutrophil elastase (neutrophil extracellular traps)
Neutrophils
The goal is to kill bacteria over a ____ area
Wider
The problem is that ____ causes lung destruction and the process creates a low O2 environment
Elastase
The low O2 environment promotes growth of _____ _____ and biofilm; once this occurs, eradication is impossible
Pseudomonas. aeruginosa
Dornase (Pulmozyme) is a drug that can decrease sputum viscosity by…
-Breaking down neutrophil extracellular traps
-Decreasing viscosity of purulent sputum
-Making secretions easier to cough up
Dornase (Pulmozyme) is administered via ____ 1-2 times per day
Nebulizer
A ____ ____ trial was done to try and decrease viscosity
Hypertonic saline
The rationale for using hypertonic saline is that it may cause…
-Excessive sodium reabsorption would draw more moisture into the airways (water follows sodium)
Result of the hypertonic saline trial:
-Higher forced vital capacity, higher forced expiratory volume
-56% fewer pulmonary exacerbations
-Osmotic effect, H2O hydrates airways
It is also important to reduce ___ ___ for patients with CF
Bacterial load
How can we prevent between patient bacterial spread?
-Contact precautions
-Physical separation of patients
-Masks in health care settings
-Good hand hygiene
We can use ____ to reduce airway inflammation
Azithromycin
We can also use ___ ___ ___ if pseudomonas is present
Cyclic inhaled antibiotics
In patients with CF, we should also try to prevent ___ ___ and maintain fitness
Weight loss
Those with CF lack ____ ___, which may cause fat malabsorption and failure to thrive
GI enzymes
The median survival age in the USA is ___ years while it is ____ in Canada
40.6; 50.9
The difference between survival rates is due to…
-Earlier adoption of high-fat, high-calorie diet
-Difference in health care systems (private vs national health care)
The benefits of a lung transplant depend on…
-Lung function (clear advantage if forced expiratory volume < 40%)
-Age at transplant (better survival over age 30)
Asthma is very common and affects ___ million people including 5.5 million children
24.7
____ is defined as variable airflow limitation and airway hyperresponsiveness due to exaggerated contractile response of airways
Asthma
Asthma causes…
-Bronchoconstriction
-Airway inflammation
-Mucus secretion
